Microbicidal N-sulfonylglycin alkynyloxyphenethyl amide derivatives

ABSTRACT

The invention relates to novel pesticidally active compounds of the general formula I                    
     as well as possible isomers and mixtures of isomers thereof, 
     wherein 
     n is a number zero or one; and 
     R 1  is C 1 -C 12 alkyl that is unsubstituted or may be substituted by C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfonyl, C 3 -C 8 cycloalkyl, cyano, C 1 C 6 alkoxycarbonyl, C 3 -C 6 alkenyloxycarbonyl or by C 3 -C 6 alkynyloxycarbonyl; C 3 -C 8 cycloalkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; C 1 -C 12 haloalkyl: or a group NR 11 R 12  wherein R 11  and R 12  are each independently of the other hydrogen or C 1 -C 8 alkyl, or together are tetra- or penta-methylene; 
     R 2  and R 3  are each independently of the other hydrogen; C 1 -C 8 alkyl; C 1 -C 8 alkyl substituted by hydroxy, C 1 -C 4 alkoxy, mercapto or by C 1 -C 4 alkylthio; C 3 -C 8 alkenyl; C 3 -C 8 alkynyl; C 3 -C 8 cycloalkyl; C 3 -C 8 cycloalkyl-C 1 -C 4 alkyl; or the two groups R 2  and R 3  together with the carbon atom to which they are bonded form a three- to eight-membered ring; 
     R 4 , R 5 , R 6  and R 7  are identical or different and are each independently of the others hydrogen or C 1 -C 4 alkyl; 
     R 8  is C 1 -C 6 alkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl; 
     A is C 1 -C 6 alkylene; and 
     B is optionally mono- or poly-nuclear, unsubstituted or substituted aryl; optionally mono- or poly-nuclear, unsubstituted or substituted heteroaryl; C 4 -C 12 alkyl; or C 3 -C 8 cycloalkyl. 
     The novel compounds have plant-protecting properties and are suitable for protecting plants against infestation by phytopathogenic microorganisms.

This application is a 371 of PCT/EP98/04849 filed Aug. 05, 1998.

The present invention relates to novel a-amino acid derivatives of formula I below. It relates to the preparation of those substances and to agrochemical compositions comprising at least one of those compounds as active ingredient. The invention relates also to the preparation of the said compositions and to the use of the compounds or of the compositions in controlling or preventing the infestation of plants by phytopathogenic microorganisms, especially fungi.

The invention relates to compounds of the general formula I

as well as possible isomers and mixtures of isomers thereof,

wherein

n is a number zero or one; and

R₁ is C₁-C₁₂alkyl that is unsubstituted or may be substituted by C₁-C₄alkoxy, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, C₃-C₈cycloalkyl, cyano, C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl or by C₃-C₆alkynyloxycarbonyl; C₃-C₈cycloalkyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl; or a group NR₁₁R₁₂ wherein R₁₁ and R₁₂ are each independently of the other hydrogen or C₁-C₆alkyl, or together are tetra- or penta-methylene;

R₂ and R₃ are each independently of the other hydrogen; C₁-C₈alkyl; C₁-C₈alkyl substituted by hydroxy, C₁-C₄alkoxy, mercapto or by C₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl; C₃-C₈cycloalkyl; C₁-C₄alkyl; or the two groups R₂ and R₃ together with the carbon atom to which they are bonded form a three- to eight-membered ring;

R₄, R₅, R₆ and R₇ are identical or different and are each independently of the others hydrogen or C₁-C₄alkyl;

R₈ is C₁-C₆alkyl, C₃-C₆alkenyl or C₃-C₆alkynyl;

A is C₁-C₆alkylene; and

B is optionally mono- or poly-nuclear, unsubstituted or substituted aryl; optionally mono- or poly-nuclear, unsubstituted or substituted heteroaryl; C₄-C₁₂alkyl; or C₃-C₈cycloalkyl.

Examples of aryl in the above-mentioned sense are:

phenyl, naphthyl, anthracenyl, phenanthrenyl.

Examples of heteroaryl are:

furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl, naphthyridinyl.

Examples of substituents of those aryl or heteroaryl groups are:

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, phenyl, phenyl-alkyl, it being possible for those groups to carry one or more identical or different halogen atoms; alkoxy; alkenyloxy; alkynyloxy; alkoxyalkyl; haloalkoxy, alkylthio; haloalkylthio; alkylsulfonyl; formyl; alkanoyl; hydroxy; halogen; cyano; nitro; amino; alkylamino; dialkylamino; carboxy; alkoxycarbonyl; alkenyloxycarbonyl; alkynyloxycarbonyl.

In the above formula I, “halogen” includes fluorine, chlorine, bromine and iodine.

The alkyl, alkenyl and alkynyl radicals may be straight-chain or branched, and this applies also to the alkyl, alkenyl or alkynyl moiety of other alkyl-, alkenyl- or alkynyl-containing groups.

Depending upon the number of carbon atoms mentioned, alkyl on its own or as part of another substituent is to be understood as being, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl and the isomers thereof, for example isopropyl, isobutyl, tert-butyl or sec-butyl, isopentyl or tert-pentyl. Cycloalkyl is, depending upon the number of carbon atoms mentioned, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

Depending upon the number of carbon atoms mentioned, alkenyl as a group or as a structural element of other groups is to be understood as being, for example, ethenyl, allyl, buten-2-yl, buten-3-yl, penten-1-yl, penten-3-yl, hexen-1-yl, 4-methyl-3-pentenyl or 4-methyl-3-hexenyl.

Alkynyl as a group or as a structural element of other groups is, for example, ethynyl, propyn-1-yl, propyn-2-yl, butyn-1-yl, butyn-2-yl, 1-methyl-2-butynyl, hexyn-1-yl, 1-ethyl-2-butynyl, octyn-1-yl.

A haloalkyl group may have one or more (identical or different) halogen atoms, for example CHCl₂, CH₂F, CCl₃, CH₂Cl, CHF₂, CF₃, CH₂CH₂Br, C₂Cl₅, CH₂Br, CHClBr, CF₃CH₂, etc.

The presence of at least one asymmetric carbon atom and/or at least one asymmetric sulfur atom in the compounds of formula I means that the compounds may occur in optically isomeric forms. As a result of the presence of a possible aliphatic C═C double bond, geometric isomerism may also occur. Formula I is intended to include all those possible isomeric forms and mixtures thereof.

Preference is given to compounds of formula I wherein

R₁ is C₁-C₁₂alkyl; C₃-C₈cycloalkyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl; or a group NR₁₁R₁₂ wherein R₁₁ and R₁₂ are each independently of the other hydrogen or C₁-C₆alkyl, or together are tetra- or penta-methylene;

R₂ is hydrogen;

R₃ is C₁-C₈alkyl; C₁-C₈alkyl substituted by hydroxy, C₁-C₄alkoxy, mercapto or by C₁-C₄alkyl-thio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl; or C₃-C₈cycloalkyl-C₁-C₄alkyl;

B is phenyl; naphthyl; or heteroaryl that is formed from one or two five- or six-membered rings and that may contain from 1 to 4 identical or different hetero atoms selected from nitrogen, oxygen and sulfur; wherein the phenyl, naphthyl or heteroaryl may optionally carry from 1 to 5 identical or different substituents selected from:

C₁-C₈alkyl, C₂-C₂₈alkenyl, C₂-C₈alkynyl, C₃-C₈cycloalkyl, C₃-C₈cycloalkyl-C₁-C₄alkyl, phenyl, phenyl-C₁-C₄alkyl, those groups being unsubstituted or mono- to per-halogenated and the halogen atoms being identical or different; C₁-C₈alkoxy; C₃-C₈alkenyloxy; C₃-C₈alkynyloxy; C₁-C₄alkoxy-C₁-C₄alkyl; C₁-C₈haloalkoxy; C₁-C₈alkylthio; C₁-C₈haloalkylthio; C₁-C₈alkyl-sulfonyl; formyl; C₂-C₈alkanoyl; hydroxy; halogen; cyano; nitro; amino; C₁-C₈alkylamino; C₁-C₈dialkylamino; carboxy; C₁-C₈alkoxycarbonyl; C₃-C₈alkenyloxycarbonyl; and C₃-C₈alkynyloxycarbonyl (sub-group A).

Within the scope of sub-group A, special mention should be made of those compounds of formula I wherein

R₁ is C₁-C₆alkyl; C₅-C₆cycloalkyl; C₂-C₆alkenyl; C₁-C₆haloalkyl; or a group NR₁₁R₁₂ wherein

R₁₁ and R₁₂ are each independently of the other hydrogen or C₁-C₆alkyl;

R₃ is C₁-C₈alkyl; or C₃-C₆cycloalkyl;

R₄ is hydrogen or C₁-C₄alkyl;

R₅, R₆ and R₇ are hydrogen;

R₈ is C₁-C₆alkyl;

A is C₁-C₂alkylene; and

B is phenyl, naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyi, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzothiazolyl or benzoxazolyl, each unsubstituted or substituted by from 1 to 5 substituents selected from: C₁-C₈alkyl, C₂-C₈alkenyl, C₂-C₈alkynyl, C₃-C₈cycloalkyl, C₃-C₈-cycloalkyl-C₁-C₄alkyl, phenyl, phenyl-C₁-C₄alkyl, those groups being unsubstituted or mono- to per-halogenated and the halogen atoms being identical or different; C₁-C₈alkoxy; C₃-C₈-alkenyloxy; C₃-C₈alkynyloxy; C₁-C₄alkoxy-C₁-C₄alkyl; C₁-C₈haloalkoxy; C₁-C₈alkylthio; C₁-C₈-haloalkylthio; C₁-C₈alkylsulfonyl; formyl; C₂-C₈alkanoyl; hydroxy; halogen; cyano; nitro; amino; C₁-C₈alkylamino; C₁-C₈dialkylamino; carboxy; C₁-C₈alkoxycarbonyl; C₃-C₈alkenyl-oxycarbonyl; and C₃-C₈alkynyloxycarbonyl (sub-group B).

Within the scope of sub-group B, special preference is given to a group of compounds of formula I wherein

n is the number one;

R₁ is C₁-C₆alkyl; C₁-C₆haloalkyl; or a group NR₁₁R₁₂ wherein R₁₁ and R₁₂ are each independently of the other C₁-C₄alkyl;

R₃ is C₃-C₄alkyl; or cyclopropyl;

R₄ is hydrogen or methyl;

R₈ is C₁-C₂alkyl;

A is methylene; and

B is phenyl, naphthyl, furyl, thienyl, pyridyl, pyrimidinyl, triazinyl, benzothiophenyl, each unsubstituted or substituted by from 1 to 3 substituents selected from: C₁-C₈alkyl, phenyl, those groups being unsubstituted or mono- to per-halogenated and the halogen atoms being identical or different; C₁-C₈alkoxy; C₃-C₈alkenyloxy; C₃-C₈alkynyloxy; C₁-C₈haloalkoxy; C₁-C₈alkylthio; C₁-C₈haloalkylthio; C₁-C₈alkylsulfonyl; formyl; C₁-C₈alkanoyl; hydroxy; halogen; cyano; nitro; and C₁-C₈alkoxycarbonyl (sub-group Ca).

A special group within the scope of sub-group Ca comprises compounds of formula I wherein

R₁ is C₁-C₄alkyl; or dimethylamino;

R₃ is 2-propyl;

R₈ is methyl;

B is phenyl, naphthyl, each unsubstituted or substituted by from 1 to 3 substituents selected from: C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio, C₁-C₈haloalkylthio, halogen, cyano, nitro and C₁-C₈alkoxycarbonyl (sub-group Cb).

Another especially preferred group within the scope of sub-group Ca comprises compounds of formula I wherein

R₁ is C₁-C₄alkyl; or dimethylamino;

R₃ is 2-propyl;

R₈ is methyl;

B is thienyl, pyridyl, each unsubstituted or substituted by from 1 to 3 substituents selected from: C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio, C₁-C₈haloalkylthio, halogen, cyano, nitro and C₁-C₈alkoxycarbonyl (sub-group Cc).

Certain α-amino acid derivatives having a different kind of structure have already been proposed for controlling plant-destructive fungi (for example in EP-398 072, EP-425 925, DE-4 026 966, EP-477 639, EP493 683, DE-4 035 851, EP-487 154, EP-496 239, EP-550 788 and EP-554 729). The action of those preparations is not, however, satisfactory. Surprisingly, with the compound structure of formula I, new kinds of microbicides having a high level of activity have been found.

The compounds of formula I can be prepared as follows:

a) by reacting a substituted amino acid of formula II

 wherein the radicals R₁ R₂ and R₃ and n are as defined above, or a carboxy-activated derivative thereof, if desired in the presence of a catalyst, if desired in the presence of an acid-binding agent and if desired in the presence of a diluent,

with an amine of formula III

 wherein R₄, R₅, R₆, R₇, R₈, A and B are as defined above.

The amino acid derivatives of formula II required for carrying out Process a) according to the invention are known per se.

The amines of formula III are novel and the invention relates also thereto.

The amines of formula III can be prepared in accordance with Process aa) described below.

Suitable carboxy-activated derivatives of the amino acid of formula II include any carboxy-activated derivatives, such as acid halides, for example acid chlorides; also symmetrical or mixed anhydrides, for example the mixed O-alkylcarboxylic acid anhydrides; and also activated esters, for example p-nitrophenyl esters or N-hydroxysuccinimide esters, and activated forms of the amino acid produced in situ using condensing agents, e.g. dicyclohexylcarbodiimide, carbonyldiimidazole, O-(benzotriazol-1-yl)-N,N,N′,N′-bis(pentamethylene)uronium hexafluorophosphate, O-(benzotriazol-1-yl)-N ,N ,N′,N′-bis(tetramethylene)uronium hexafluorophosphate, (benzotriazol-1-yloxy)-tripyrrolidinophosphonium hexafluorophosphate, (benzotriazol-1-yloxy)-tris(dimethylamino)phosphonium hexafluorophosphate or O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate.

The mixed anhydrides corresponding to the amino acid of formula II can be prepared by reacting the amino acid of formula II with a chloroformic acid ester, for example a chloroformic acid alkyl ester, preferably isobutyl chloroformate, if desired in the presence of an acid-binding agent, such as an inorganic or organic base, for example a tertiary amine, e.g. triethylamine, pyridine, N-methylpiperidine or N-methylmorpholine.

The reaction of the amino acid of formula II, or of a carboxy-activated derivative of the amino acid of formula II, with an amine of formula III is carried out in an inert diluent, such as an aromatic, non-aromatic or halogenated hydrocarbon, for example a chlorinated hydrocarbon, e.g. methylene chloride or toluene; a ketone, e.g. acetone; an ester, e.g. ethyl acetate; an amide, e.g. dimethylformamide; a nitrile, e.g. acetonitrile; or an ether, e.g. tetrahydrofuran, dioxane, diethyl ether or tert-butyl methyl ether; or in a mixture of those inert diluents, if desired in the presence of an acid-binding agent, such as an inorganic or organic base, for example a tertiary amine, e.g. triethylamine, pyridine, N-methylpiperidine or N-methylmorpholine, at temperatures of from −80 to +150° C., preferably from −40 to +40° C.

b) by oxidising a compound of formula I′

 wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, A and B are as defined above, with the proviso that none of the substituents R₁, R₂, R₃ and B contains a thiol or alkylthio group.

Suitable oxidising agents include both organic oxidising agents, such as alkyl hydroperoxides, for example cumyl hydroperoxide, and inorganic oxidising agents, such as peroxides, for example hydrogen peroxide, and transition metal oxides, for example chromium trioxide, and transition metal oxide salts, for example potassium permanganate, potassium dichromate or sodium dichromate.

The reaction of a compound of formula I′ with an oxidising agent is carried out in an inert diluent, such as water or a ketone, for example acetone, or in a mixture of those inert diluents, if desired in the presence of an acid or it desired in the presence of a base, at temperatures of from −80 to +150° C.

c) by reacting a compound of formula IV

 wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈ and n are as defined above, with a compound of formula V

Y—A—≡—B  V

wherein A and B are as defined above and wherein Y is a leaving group.

Suitable leaving groups include halides, for example chlorides or bromides, and sulfonates, for example tosylates, mesylates or triflates.

The reaction of a compound of formula IV with a compound of formula V is carried out in an inert diluent. The following may be mentioned as examples: aromatic, non-aromatic or halogenated hydrocarbons, e.g. toluene or methylene chloride; ketones, e.g. acetone; esters, e.g. ethyl acetate; amides, e.g. dimethylformamide; nitrites, e.g. acetonitrile; ethers, e.g. tetrahydrofuran, dioxane, diethyl ether or tert-butyl methyl ether; alcohols, e.g. methanol, ethanol, n-butanol, isopropanol or tert-butanol; dimethyl sulfoxide; or water; or mixtures of those inert diluents. The reaction of a compound of formula IV with a compound of formula V is carried out if desired in the presence of an acid-binding agent. Suitable acid-binding agents include inorganic or organic bases, for example alkali metal or alkaline earth metal hydroxides, alcoholates or carbonates, e.g. sodium hydroxide, potassium hydroxide, sodium methanolate, potassium methanolate, sodium ethanolate, potassium ethanolate, sodium tert-butanolate, potassium tert-butanolate, sodium carbonate or potassium carbonate. The temperatures are from −80 to +200° C., preferably from 0 to +120° C.

d) by reacting a sulfonic acid or sulfinic acid, or a sulfonic acid or sulfinic acid derivative, of formula VI

 wherein R₁ and n are as defined above and wherein X is an OH group or a leaving group, respectively, with an amine of formula VII

 wherein R₂, R₃, R₄, R₅, R₆, R₇, R₈, A and B are as defined above.

The invention relates also to compounds of formula VII and to their preparation.

The sulfonic acid or sulfinic acid, or sulfonic acid or sulfinic acid derivatives, of formula VI required for Process d) are known parse. The amines of formula VII also required are novel and the invention relates also thereto; they can be prepared in accordance with Process bb) below.

Suitable sulfonic acid or sulfinic acid derivatives of formula VI include any compounds wherein X is a leaving group, such as sulfonic acid halides or sulfinic acid halides, e.g. sulfochlorides or sulfinic acid chlorides; also symmetrical or mixed anhydrides; and also activated forms of sulfonic acid or sulfinic acid produced in situ using condensing agents, such as dicyclohexylcarbodiimide or carbonyldiimidazole.

The reaction of the sulfonic acid or sulfinic acid, or of the sulfonic acid or sulfinic acid derivative, of formula VI with an amine of formula VII is carried out in an inert diluent, such as an aromatic, non-aromatic or halogenated hydrocarbon, for example a chlorinated hydrocarbon, e.g. methylene chloride or toluene; a ketone, e.g. acetone; an ester, e.g. ethyl acetate; an amide, e.g. dimethylformamide; a nitrile, e.g. acetonitrile; or an ether, e.g. tetrahydrofuran, dioxane, diethyl ether or tert-butyl methyl ether; or water; or in a mixture of those inert diluents, if desired in the presence of an acid-binding agent, such as an inorganic or organic base: for example an alkali metal or alkaline earth metal hydroxide or carbonate, e.g. sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate, or, for example, a tertiary amine, e.g. triethylamine, pyridine, N-methylpiperidine or N-methylmorpholine, at temperatures of from −80 to +150° C., preferably from −20 to +60° C.

e) by reacting an alkyne of formula I″

 wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, A and n are as defined above, with an aryl or heteroaryl halide, preferably an aryl or heteroaryl iodide.

Alkynes of formula I″ are known, for example, from WO 95/30651.

The reaction of the alkyne of formula I″ with an aryl or heteroaryl halide is carried out in an inert diluent, such as an aromatic, non-aromatic or halogenated hydrocarbon, for example a chlorinated hydrocarbon, e.g. methylene chloride, chloroform or toluene; an amide, e.g. dimethylformamide; an ether, e.g. dioxane or tetrahydrofuran; or a sulfoxide, e.g. dimethyl sulfoxide; or in a mixture of those inert diluents, if desired in the presence of an acid-binding agent, such as an inorganic or organic base, for example a tertiary amine, e.g. triethylamine, N-methylpiperidine or pyridine, if desired in the presence of one or more transition metal salts, for example a copper halide or palladium halide, e.g. copper iodide or palladium dichloride, and if desired in the presence of one or more transition metal complexes or transition metal complex salts, such as a bis(triaryl- or trialkyl-)palladium dihalide, e.g. bis(triphenylphosphine)palladium dichloride, at temperatures of from −80 to +200° C., preferably from 0 to +60° C.

Important intermediates can be prepared as follows:

aa) The amines of formula III can be prepared in accordance with the following process variants:

Step A comprises the alkylation of a phenol with a compound of formula V. The reaction is carried out as described under Process c).

Step B comprises the reaction of an aromatic aldehyde with nitromethane. The reaction of the two reactants is carried out in an inert diluent, such as an organic carboxylic acid, for example acetic acid, optionally in the presence of the ammonium salt of that carboxylic acid, for example ammonium acetate, at temperatures of from 0° to +200° C.

Step C comprises the reduction of an unsaturated nitrogen compound. The reaction is carried out in an inert diluent, such as an ether, for example diethyl ether, dioxane or tetrahydrofuran, or an alcohol, for example methanol, ethanol or isopropanol, with boron hydride, a boron hydride complex, for example the complex of boron hydride and tetrahydrofuran, an alkali metal borohydride, an alkali metal aluminum hydride, for example lithium aluminum hydride, or an aluminum alkoxyhydride, or with hydrogen if desired in the presence of a transition metal or a transition metal compound, for example nickel, at temperatures of from −50° to +250° C.

Step D comprises the reaction of an aldehyde or a ketone with hydroxylamine or a hydroxylamine salt. The reaction is carried out in an inert diluent, such as an alcohol, for example methanol, ethanol or isopropanol, an ether, for example diethyl ether, dioxane or tetrahydrofuran, an amide, for example dimethylformamide, or in water, or in a mixture of those inert diluents, if desired in the presence of an organic or inorganic base, such as a tertiary amine, for example triethylamine, a nitrogen-containing heteroaromatic compound, for example pyridine, an alkali metal or alkaline earth metal carbonate or hydrogen carbonate, for example sodium carbonate or potassium carbonate, at temperatures of from −20° to +150° C.

Step E comprises the hydrolysis of a lower alkyl ester. The reaction is carried out in an inert diluent, such as an alcohol, for example methanol, ethanol or isopropanol, an ether, for example diethyl ether, dioxane or tetrahydrofuran, a halogenated hydrocarbon, for example dichloromethane, or in water, or in a mixture of those inert diluents, if desired in the presence of a base, such as an alkali metal or alkaline earth metal hydroxide, for example lithium hydroxide, sodium hydroxide or potassium hydroxide, or in the presence of an acid, for example sulfuric acid, hydrochloric acid or trifluoroacetic acid, at temperatures of from −20° to +160° C.

Step F comprises the reaction of a carboxylic acid or an activated derivative of that carboxylic acid with hydrazoic acid or with a salt of that acid. Suitable carboxy-activated derivatives include any carboxy-activated derivatives, such as acid halides, for example acid chlorides; and also symmetrical or mixed anhydrides, for example the mixed O-alkylcarboxylic acid anhydrides. Suitable salts of hydrazoic acid include, for example, alkali metal or alkaline earth metal azides, for example sodium azide. The reaction is carried out in a diluent, such as a hydrocarbon, for example toluene or xylene, a halogenated hydrocarbon, for example chloroform, an ether, for example dioxane, a ketone, for example acetone or methyl ethyl ketone, an alcohol, for example tert-butanol, or in water, or in a mixture of those diluents, if desired in the presence of an acid, such as an inorganic acid, for example sulfuric acid or hydrochloric acid, at temperatures of from −40° to +200° C.

bb) The required amines of formula VII can be prepared in accordance with the following reaction sequence

In a first step, an amino acid derivative of the general formula XIII, or a carboxy-activated derivative thereof, is reacted, if desired in the presence of a catalyst, if desired in the presence of an acid-binding agent and if desired in the presence of a diluent, with an amine of the general formula XII.

Suitable carboxy-activated derivatives of the amino acid of formula XIII include any carboxy-activated derivatives, such as acid halides, for example acid chlorides; also symmetrical or mixed anhydrides, for example the mixed O-alkylcarboxylic acid anhydrides; and also activated esters, for example p-nitrophenyl esters or N-hydroxysuccinimide esters, and activated forms of the amino acid produced in situ using condensing agents, e.g. dicyclohexylcarbodiimide, carbonyldiitmidazole, O-(benzotriazol-yl)-N,N, N′,N′-bis(pentamethylene)uronium hexafluorophosphate, O-(benzotriazo-1-yl)-N,N,N′,N′-bis(tetra-methylene)uronium hexafluorophosphate, (benzotriazol-1-yloxy)-tripyrrolidinophosphonium hexafluorophosphate, (benzotriazol-1-yloxy)-tris(dimethylamino)phosphonium hexafluorophosphate or O-(benzotriazol-1-yl)-N,N,N′,N′-tetramnethyluronium hexafluorophosphate.

The mixed anhydrides corresponding to the amino acid of formula XIII can be prepared by reacting the amino acid of formula XIII with a chloroformic acid ester, for example a chloroformic acid alkyl ester, preferably isobutyl chloroformate, i desired in the presence of an acid-binding agent, such as an inorganic or organic base, for example a tertiary amine, e.g. triethylamine, pyridine, N-methylpiperidine or N-methylmorpholine.

The reaction of the amino acid of formula XIII, or of a carboxy-activated derivative of the amino acid of formula XIII, with an amine of formula XII is carried out in an inert diluent, such as an aromatic, non-aromatic or halogenated hydrocarbon, for example a chlorinated hydrocarbon, e.g. methylene chloride or toluene; a ketone, e.g. acetone; an ester, e.g. ethyl acetate; an amide, e.g. dimethylformamide; a nitrile, e.g. acetonitrile; or an ether, e.g. tetrahydrofuran, dioxane, diethyl ether or tert-butyl methyl ether; or in a mixture of those inert difuents, if desired in the presence of an acid-binding agent, e.g. an inorganic or organic base, for example a tertiary amine, e.g. triethylamine, pyrdine, N-methylpiperidine or N-methylmorpholine, at temperatures of from −80 to +150° C., preferably from −40 to +40° C.

In a second step, a compound of formula XIV is reacted with a compound of formula V.

The reaction of a compound of formula XIV with a compound of formula V is carried out in an inert diluent. The following may be mentioned as examples: aromatic, non-aromatic or halogenated hydrocarbons, for example toluene or methylene chloride; ketones, for example acetone; esters, for example ethyl acetate; amides, for example dimethylformamide; nitriles, for example acetonitrile; ethers, for example tetrahydrofuran, dioxane, diethyl ether or tert-butyl methyl ether; alcohols, for example methanol, ethanol, n-butanol, isopropanol or tert-butanol; dimethyl sulfoxide; or water; or mixtures of those inert diluents. The reaction of a compound of formula XIV with a compound of formula V is carried out if desired in the presence of an acid-binding agent. Suitable acid-binding agents include inorganic or organic bases, for example alkali metal or alkaline earth metal hydroxides, alcoholates or carbonates, e.g. sodium hydroxide, potassium hydroxide, sodium methanolate, potassium methanolate, sodium ethanolate, potassium ethanolate, sodium tertbutanolate, potassium tert-butanolate, sodium carbonate or potassium carbonate. The temperatures are from −80 to +200° C., preferably from 0 to +120° C.; or the reaction is carried out as described under Process c).

In a third step, compounds of formula XV are subjected to acid hydrolysis. The reaction of a compound of formula XV with an inorganic or organic acid, for example a mineral acid, e.g. hydrochloric acid or sulfuric acid, or a carboxylic acid, e.g. acetic acid or trifluoroacetic acid, or a sulfonic acid, e.g. methanesulfonic acid or p-toluenesulfonic acid, is carried out if desired in an inert diluent, such as an aromatic, non-aromatic or halogenated hydrocarbon, for example a chlorinated hydrocarbon, e.g. methylene chloride or toluene; a ketone, e.g. acetone; an ester, e.g. ethyl acetate; an ether, e.g. tetrahydrofuran or dioxane; or water, at temperatures of from −40 to +150° C. It desired, it is also possible to use mixtures of different acids and of different inert diluents, or the acid itself may serve as the diluent.

The compounds of formula I are oils or solids at room temperature and are distinguished by valuable microbicidal properties. They can be used in the agricultural sector or related fields preventively and curatively in the control of plant-destructive microorganisms. The compounds of formula I according to the invention are distinguished at low rates of concentration not only by outstanding microbicidal, especially fungicidal, activity but also by being especially well tolerated by plants.

Surprisingly, it has now been found that the compounds of formula I have for practical purposes a very advantageous biocidal spectrum in the control of phytopathogenic microorganisms, especially fungi. They possess very advantageous curative and preventive properties and are used in the protection of numerous crop plants. With the compounds of formula I it is possible to inhibit or destroy phytopathogenic microorganisms that occur on various crops of useful plants or on parts of such plants (fruit, blossom, leaves, stems, tubers, roots), while parts of the plants which grow later also remain protected, for example, against phytopathogenic fungi.

The novel compounds of formula I prove to be effective against specific genera of the fungus class Fungi imperfecti (e.g. Cercospora), Basidiomycetes (e.g. Puccinia) and Ascomycetes (e.g. Erysiphe and Venturia) and especially against Oomycetes (e.g. Plasmopara, Peronospora, Pythium and Phytophthora). They therefore represent in plant protection a valuable addition to the compositions for controlling phytopathogenic fungi. The compounds of formula I can also be used as dressings for protecting seed (fruit, tubers, grains) and plant cuttings from fungal infections and against phytopathogenic fungi that occur in the soil.

The invention relates also to compositions comprising compounds of formula I as active ingredient, especially plant-protecting compositions, and to the use thereof in the agricultural sector or related fields.

In addition, the present invention includes the preparation of those compositions, wherein the active ingredient is homogeneously mixed with one or more of the substances or groups of substances described herein. Also included is a method of treating plants which is distinguished by the application of the novel compounds of formula I or of the novel compositions.

Target crops to be protected within the scope of this invention comprise, for example, the following species of plants: cereals (wheat, barley, rye, oats, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, stone fruit and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucurbitaceae (marrows, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamon, camphor) and plants such as tobacco, nuts, coffee, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, and also ornamentals.

The compounds of formula I are normally used in the torm of compositions and can be applied to the area or plant to be treated simultaneously or in succession with other active ingredients. Those other active ingredients may be fertilisers, micronutrient donors or other preparations that influence plant growth. It is also possible to use selective herbicides or insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of those preparations, if desired together with further carriers, surfactants or other application-promoting adjuvants customarily employed in formulation technology.

The compounds of formula I can be mixed with other active ingredients, for example fertilisers, micronutrient donors or other crop protection products, especially other fungicides, with the result that unexpected synergistic effects may occur. Preferred mixing partners are: azoles, such as azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazole, metconazole, myclobutanil, pefurazoate, penconazole, pyrifenox, prochloraz, propiconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triflumizole, triticonazole;

pyrimidinyl carbinols, such as ancymidol, fenarimol, nuarimol;

2-amino-pyrimidines, such as bupirimate, dimethirimol, ethirimol;

morpholines, such as dodemorph, fenpropidin, fenpropimorph, spiroxamin, tridemorph;

anilinopyrimidines, such as cyprodinil, mepanipyrim, pyrimethanil;

pyrroles, such as fenpiclonil, fludioxonil;

phenylamides, such as benalaxyl, furalaxyl, metalaxyl, R-metalaxyl, ofurace, oxadixyl;

benzimidazoies, such as benomyl, carbendazim, debacarb, fuberidazole, thiabendazole; dicarboximides, such as chlozolinate, dichlozoline, iprodione, myclozoline, procymidone, vinclozolin;

carboxamides, such as carboxin, fenturam, flutolanil, mepronil, oxycarboxin, thifluzamide;

guanidines, such as guazatine, dodine, iminoctadine;

strobilurines, such as azoxystrobin, kresoxim-methyl, metominostrobin, SSF-129, CGA 279202;

dithiocarbamates, such as ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb, ziram;

N-halomethylthio, such as captafol, captan, dichlofluanid, fluoromide, folpet, tolyfluanid; copper compounds, such as Bordeaux mixture, copper hydroxide, copper oxychloride,

copper sulfate, cuprous oxide, mancopper, oxine-copper;

nitrophenol derivatives, such as dinocap, nitrothal-isopropyl;

organo-P derivatives, such as edifenphos, iprobenphos, isoprothiolane, phosdiphen, pyrazophos, tolclofos-methyl;

various others, such as acibenzolar-S-methyl, anilazine, blasticidin-S, chinomethionat, chloroneb, chlorothalonil, cymoxanil, dichlone, diclomezine. dicloran, diethofencarb, dimethomorph, dithianon, etridiazole, famoxadone, fentin, ferimzone, fluazinam, flusulfamide, fenhexamid, fosetyl-aluminum, hymexazol, kasugamycin, methasulfocarb, pencycuron, phthalide, polyoxins, probenazole, propamocarb, pyroquilon, quinoxyfen, quintozene, sulfur, triazoxide, tricyclazole, triforine, validamycin.

Suitable carriers and surfactants may be solid or liquid and correspond to the substances ordinarily employed in formulation technology, such as e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilisers. Such carriers and additives are described, for example, in WO 95/30651.

A preferred method of applying a compound of formula I, or an agrochemical composition comprising at least one of those compounds, is application to the foliage (foliar application), the frequency and the rate of application depending upon the risk of infestation by the pathogen in question. The compounds of formula I may also be applied to seed grains (coating) either by impregnating the grains with a liquid formulation of the active ingredient or by coating them with a solid formulation.

The compounds of formula I are used in unmodified form or, preferably, together with the adjuvants conventionally employed in formulation technology, and are for that purpose advantageously formulated in known manner e.g. into emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granules, and by encapsulation in e.g. polymer substances. As with the nature of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.

Advantageous rates of application are normally from 1 g to 2 kg of active ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kg a.i./ha, especially from 25 g to 750 g a.i./ha. When used as seed dressings, rates of from 0.001 g to 1.0 g of active ingredient per kg of seed are advantageously used.

The formulations, i.e. the compositions, preparations or mixtures comprising the compound(s) (active ingredient(s)) of formula I and, where appropriate, a solid or liquid adjuvant, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredient with extenders, e.g. solvents, solid carriers and, where appropriate, surface-active compounds (surfactants).

Further surfactants customarily used in formulation technology will be known to the person skilled in the art or can be found in the relevant technical literature.

The agrochemical compositions usually comprise 0.01 to 99% by weight, preferably 0.1 to 95% by weight, of a compound of formula 1, 99.99 to 1% by weight, preferably 99.9 to 5% by weight, of a solid or liquid adjuvant, and 0 to 25% by weight, preferably 0.1 to 25% by weight, of a surfactant.

Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.

The compositions may also comprise further ingredients, such as stabilisers, antifoams, viscosity regulators, binders and tackifiers, as well as fertilisers or other active ingredients for obtaining special effects.

The Examples which follow illustrate the invention described above, without limiting the scope thereof in any way. Temperatures are given in degrees Celsius.

PREPARATION EXAMPLES FOR COMPOUNDS OF FORMULA I: Example 1.001

(S)-2-(Methylsultonyl-amino)-3-methyl-butyric acid N-{2-[3-methoxy-4-(3-phenyl-2-propyn-1-yloxy)-phenyl]-ethyl}-amide

2.5 g of (S)-2-(methylsulfonyl-amino)-3-methyl-butyric acid N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-amide and 2.7 g of toluene-4-sulfonic acid (3-phenyl-2-propyn-1-yl) ester are heated at reflux for 3 hours together with 12 ml of 1M sodium methanolate solution with the addition of 20 mg of potassium iodide in 50 ml of methanol. The reaction mixture is cooled and introduced into 200 ml of saturated sodium chloride solution. Extraction is carried out twice using 200 ml of ethyl acetate each time. The organic phases are combined, dried over magnesium sulfate and concentrated. The residue is subjected to flash chromatography on silica gel with ethyl acetate/n-hexane (2:1), yielding (S)-2-(methylsulfonyl-amino)-3-methyl-butyric acid N-{2-[3-methoxy-4-(3-phenyl-2-propyn-1-yloxy)-phenyl]-ethyl}-amide, which is recrystallised from ethyl acetate/n-hexane, m.p. 130-132° C.

The Examples listed in Table 1 are obtained in an analogous manner.

TABLE 1

Phys. Comp. data No. R₁ R₂ R₃ α-C R₄ R₈ A B m.p. ° C. 1.001 Me H 2-propyl S H Me —CH₂— phenyl 130-132 1.002 Me H 2-propyl S H Me —CH₂— 4-Me-phenyl 1.003 Me H 2-propyl S H Me —CH₂— 4-Cl-phenyl 111-113 1.004 Me H 2-propyl S H Me —CH₂— 3-Me-phenyl 1.005 Me H 2-propyl S H Me —CH₂— 3-Cl-phenyl 1.006 Me H 2-propyl S H Me —CH₂— 2-Me-phenyl 1.007 Me H 2-propyl S H Me —CH₂— 4-MeO-phenyl 1.008 Me H 2-propyl S H Me —CH₂— 4-CF₃-phenyl 1.009 Me H 2-propyl S H Me —CH₂— 4-CH₃CO-phenyl 1.010 Me H 2-propyl S H Me —CH₂— 3,5-di-CF₃- resin phenyl 1.011 Me H 2-propyl S H Me —CH₂— 2-pyridyl 1.012 Me H 2-propyl S H Me —CH₂— 3-pyridyl 1.013 Me H 2-propyl S H Me —CH₂— 4-pyridyl 1.014 Me H 2-propyl S H Me —CH₂— 2-thienyl 1.015 Me H 2-propyl S Me Me —CH₂— phenyl 1.016 Me H 2-propyl S H allyl —CH₂— phenyl 1.017 Me H 2-propyl S H Me —CH(CH₃)— phenyl 1.018 Me H 2-propyl S H Me —C(CH₃)₂— phenyl 1.019 Me Me Me — H Me —CH₂— phenyl 1.020 Me tetramethylene — H Me —CH₂— phenyl 1.021 Me H Et S H Me —CH₂— phenyl 1.022 Me H Et S H Me —CH₂— phenyl 1.023 Me H Et S H Me —CH₂— phenyl 1.024 Me H cyclo- R,S H Me —CH₂— phenyl propyl 1.025 Me H cyclo- S H Me —CH₂— phenyl propyl 1.026 Me H 2-butyl S H Me —CH₂— phenyl 1.027 Me H 2-Me-2- S H Me —CH₂— phenyl propyl 1.028 Me H cyclo- R,S H Me —CH₂— phenyl hexyl 1.029 Me H cyclo- R,S H Me —CH₂— phenyl propyl- methyl 1.030 Me H 1-OH—Et S H Me —CH₂— phenyl 1.031 Me H 2-(SMe)- S H Me —CH₂— phenyl ethyl 1.032 Me H mercap- S H Me —CH₂— phenyl tomethyl 1.033 Et H 2-propyl S H Me —CH₂— phenyl 129-130 1.034 Et H 2-propyl S H Me —CH₂— 4-F-phenyl 82-83 1.035 Et H 2-propyl S H Me —CH₂— 4-Cl-phenyl 125-127 1.036 Et H 2-propyl S H Me —CH₂— 4-Br-phenyl 129-131 1.037 Et H 2-propyl S H Me —CH₂— 4-MeO-phenyl 72-75 1.038 Et H 2-propyl S H Me —CH₂— 4-NO₂-phenyl 139-142 1.039 Et H 2-propyl S H Me —CH₂— 4-CH₃OOC- 133-134 phenyl 1.040 Et H 2-propyl S H Me —CH₂— 4-CF₃-phenyl 150-152 1.041 Et H 2-propyl S H Me —CH₂— 4-CF₃O-phenyl 1.042 Et H 2-propyl S H Me —CH₂— 4-CH₃CO-phenyl 120-125 1.043 Et H 2-propyl S H Me —CH₂— 4-CN-phenyl 1.044 Et H 2-propyl S H Me —CH₂— 4-(tert-butyl)- phenyl 1.045 Et H 2-propyl S H Me —CH₂— 4-ethyl-phenyl 1.046 Et H 2-propyl S H Me —CH₂— 4-CHF₂O-phenyl 1.047 Et H 2-propyl S H Me —CH₂— 4-PhCO-phenyl 1.048 Et H 2-propyl S H Me —CH₂— 4-NH₂-phenyl 1.049 Et H 2-propyl S H Me —CH₂— 4-MeS-phenyl 1.050 Et H 2-propyl S H Me —CH₂— 3-Br-phenyl 108-110 1.051 Et H 2-propyl S H Me —CH₂— 3-F-phenyl 117-119 1.052 Et H 2-propyl S H Me —CH₂— 3-Cl-phenyl 120-122 1.053 Et H 2-propyl S H Me —CH₂— 3-MeO-phenyl 101-103 1.054 Et H 2-propyl S H Me —CH₂— 3-CF₃-phenyl 79-80 1.055 Et H 2-propyl S H Me —CH₂— 3-Me-phenyl 94-96 1.056 Et H 2-propyl S H Me —CH₂— 3-NO₂-phenyl 78-80 1.057 Et H 2-propyl S H Me —CH₂— 3-NH₂-phenyl 1.058 Et H 2-propyl S H Me —CH₂— 3-EtOOC-phenyl 1.059 Et H 2-propyl S H Me —CH₂— 3-MeOOC- phenyl 1.060 Et H 2-propyl S H Me —CH₂— 3-CN-phenyl 1.061 Et H 2-propyl S H Me —CH₂— 2-Br-phenyl 65-67 1.062 Et H 2-propyl S H Me —CH₂— 2-F-phenyl 1.063 Et H 2-propyl S H Me —CH₂— 2-Cl-phenyl 105-107 1.064 Et H 2-propyl S H Me —CH₂— 2-MeO-phenyl 1.065 Et H 2-propyl S H Me —CH₂— 2-CF₃-phenyl 115-120 1.066 Et H 2-propyl S H Me —CH₂— 2-Me-phenyl 92-94 1.067 Et H 2-propyl S H Me —CH₂— 2-NO₂-phenyl 1.068 Et H 2-propyl S H Me —CH₂— 2-CF₃O-phenyl 1.069 Et H 2-propyl S H Me —CH₂— 2-MeS-phenyl 1.070 Et H 2-propyl S H Me —CH₂— 3,4-di-F-phenyl 118-121 1.071 Et H 2-propyl S H Me —CH₂— 3,4-di-Cl-phenyl 135-137 1.072 Et H 2-propyl S H Me —CH₂— 3,4-di-Me-phenyl 127-130 1.073 Et H 2-propyl S H Me —CH₂— 3-F-4-Me-phenyl 128-131 1.074 Et H 2-propyl S H Me —CH₂— 3-Me-4-F-phenyl 1.075 Et H 2-propyl S H Me —CH₂— 3-Cl-4-Me-phenyl 139-141 1.076 Et H 2-propyl S H Me —CH₂— 3-F-4-Cl-phenyl 130-133 1.077 Et H 2-propyl S H Me —CH₂— 3-F-4-Br-phenyl 1.078 Et H 2-propyl S H Me —CH₂— 3-Me-4-Br-phenyl 1.079 Et H 2-propyl S H Me —CH₂— 3-Me-4-F-phenyl 1.080 Et H 2-propyl S H Me —CH₂— 2,4-di-Cl-phenyl 121-122 1.081 Et H 2-propyl S H Me —CH₂— 2-F-4-Br-phenyl 1.082 Et H 2-propyl S H Me —CH₂— 2,4-di-Me-phenyl 113-115 1.083 Et H 2-propyl S H Me —CH₂— 2-Cl-4-CF₃- phenyl 1.084 Et H 2-propyl S H Me —CH₂— 2-CF₃-4-Cl- phenyl 1.085 Et H 2-propyl S H Me —CH₂— 2,4-di-MeO- phenyl 1.086 Et H 2-propyl S H Me —CH₂— 2,5-di-Cl-phenyl 137-139 1.087 Et H 2-propyl S H Me —CH₂— 2-Cl-5-CF₃- 148-150 phenyl 1.088 Et H 2-propyl S H Me —CH₂— 2,5-di-Me-phenyl 1.089 Et H 2-propyl S H Me —CH₂— 2-MeO-5-Cl- phenyl 1.090 Et H 2-propyl S H Me —CH₂— 2-Me-5-Cl-phenyl 1.091 Et H 2-propyl S H Me —CH₂— 3,5-di-Cl-phenyl 154-155 1.092 Et H 2-propyl S H Me —CH₂— 3-F-5-NO₂- phenyl 1.093 Et H 2-propyl S H Me —CH₂— 3,5-di-CF₃- 145-147 phenyl 1.094 Et H 2-propyl S H Me —CH₂— 3,5-di-Me-phenyl 1.095 Et H 2-propyl S H Me —CH₂— 2,4,5-tri-Cl- 129-131 phenyl 1.096 Et H 2-propyl S H Me —CH₂— 2,3,4,5,6-penta- F-phenyl 1.097 Et H 2-propyl S H Me —CH₂— 2-pyridyl 1.098 Et H 2-propyl S H Me —CH₂— 6-Me-2-pyridyl 1.099 Et H 2-propyl S H Me —CH₂— 3-Cl-5-CF₃-2- pyridyl 1.100 Et H 2-propyl S H Me —CH₂— 5-CF₃-pyridyl 1.101 Et H 2-propyl S H Me —CH₂— 3-pyridyl 1.102 Et H 2-propyl S H Me —CH₂— 4-pyridyl 1.103 Et H 2-propyl S H Me —CH₂— 2-pyrimidinyl 1.104 Et H 2-propyl S H Me —CH₂— 4-pyrazolyl 1.105 Et H 2-propyl S H Me —CH₂— 2-thienyl 154-155 1.106 Et H 2-propyl S H Me —CH₂— 5-Me-2-thienyl 1.107 Et H 2-propyl S H Me —CH₂— 2,4,5-tri-Me- thienyl 1.108 Et H 2-propyl S H Me —CH₂— 2-benzothiazolyl 1.109 Et H 2-propyl S H Me —CH₂— 2-quinolinyl 1.110 Et H 2-propyl S Me Me —CH₂— phenyl 1.111 Et H 2-propyl S H allyl —CH₂— phenyl 1.112 Et H 2-propyl S H Me —CH(CH₃) phenyl 1.113 Et H 2-propyl S H Me —C(CH₃)₂— phenyl 1.114 Et Me Me — H Me —CH₂— phenyl 1.115 Et tetramethylene — H Me —CH₂— phenyl 1.116 Et H Et S H Me —CH₂— phenyl 1.117 Et H Et S H Me —CH₂— phenyl 1.118 Et H Et S H Me —CH₂— phenyl 1.119 Et H cyclo- R,S H Me —CH₂— phenyl propyl 1.120 Et H cyclo- S H Me —CH₂— phenyl propyl 1.121 Et H 2-butyl S H Me —CH₂— phenyl 1.122 Et H 2-Me-2- S H Me —CH₂— phenyl propyl 1.123 Et H cyclo- R,S H Me —CH₂— phenyl hexyl 1.124 Et H cyclo- R,S H Me —CH₂— phenyl propyl- methyl 1.125 Et H 1-OH—Et S H Me —CH₂— phenyl 1.126 Et H 2-(SMe)- S H Me —CH₂— phenyl ethyl 1.127 Et H mercap- S H Me —CH₂— phenyl tomethyl 1.128 Me₂N H 2-propyl S H Me —CH₂— phenyl 96-98 1.129 Me₂N H 2-propyl S H Me —CH₂— 4-Cl-phenyl 135-137 1.130 Me₂N H 2-propyl S H Me —CH₂— 4-CF₃-phenyl 1.131 Me₂N H 2-propyl S H Me —CH₂— 4-CF₃O-phenyl 1.132 Me₂N H 2-propyl S H Me —CH₂— 4-CHF₂-phenyl 1.133 Me₂N H 2-propyl S H Me —CH₂— 3-Cl-phenyl 1.134 Me₂N H 2-propyl S H Me —CH₂— 3-CF₃-phenyl 1.135 Me₂N H 2-propyl S H Me —CH₂— 3-Me-phenyl 1.136 Me₂N H 2-propyl S H Me —CH₂— 3,5-di-CF₃- resin phenyl 1.137 Me₂N H 2-propyl S H Me —CH₂— 2-pyridyl 1.138 Me₂N H 2-propyl S H Me —CH₂— 3-Cl-5-CF₃-2- pyridyl 1.139 Me₂N H 2-propyl S H Me —CH₂— 5-CF₃-pyridyl 1.140 Me₂N H 2-propyl S H Me —CH₂— 4-pyrazolyl 1.141 Me₂N H 2-propyl S H Me —CH₂— 2-thienyl 1.142 Me₂N H 2-propyl S Me Me —CH₂— phenyl 1.143 Me₂N H 2-propyl S H allyl —CH₂— phenyl 1.144 Me₂N H 2-propyl S H Me —CH(CH₃) phenyl 1.145 Me₂N H 2-propyl S H Me —C(CH₃)₂— phenyl 1.146 Me₂N Me Me — H Me —CH₂— phenyl 1.147 Me₂N tetramethylene — H Me —CH₂— phenyl 1.148 Me₂N H Et S H Me —CH₂— phenyl 1.149 Me₂N H Et S H Me —CH₂— phenyl 1.150 Me₂N H Et S H Me —CH₂— phenyl 1.151 Me₂N H cyclo- R,S H Me —CH₂— phenyl propyl 1.152 Me₂N H cyclo- S H Me —CH₂— phenyl propyl 1.153 Me₂N H 2-butyl S H Me —CH₂— phenyl 1.154 Me₂N H 2-Me-2- S H Me —CH₂— phenyl propyl 1.155 Me₂N H cyclo- R,S H Me —CH₂— phenyl hexyl 1.156 Me₂N H cyclo- R,S H Me —CH₂— phenyl propyl- methyl 1.157 Me₂N H 1-OH—Et S H Me —CH₂— phenyl 1.158 Me₂N H 2-(SMe)- S H Me —CH₂— phenyl ethyl 1.159 Me₂N H mercap- S H Me —CH₂— phenyl tomethyl 1.160 isopropyl H 2-propyl S Me Me —CH₂— phenyl 1.161 isopropyl H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 1.162 isopropyl H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- phenyl 1.163 propyl H 2-propyl S Me Me —CH₂— phenyl 1.164 propyl H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 1.165 propyl H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- phenyl 1.166 3-Cl- H 2-propyl S Me Me —CH₂— phenyl propyl 1.167 3-Cl- H 2-propyl S Me Me —CH₂— 4-Cl-phenyl propyl 1.168 3-Cl- H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- propyl phenyl 1.169 CF₃ H 2-propyl S Me Me —CH₂— phenyl 1.170 CF₃ H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 1.171 CF₃ H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- phenyl 1.172 CF₃CH₂ H 2-propyl S Me Me —CH₂— phenyl 1.173 CF₃CH₂ H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 1.174 CF₃CH₂ H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- phenyl 1.175 MeHN H 2-propyl S Me Me —CH₂— phenyl 1.176 MeHN H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 1.177 MeHN H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- phenyl 1.178 ethenyl H 2-propyl S Me Me —CH₂— phenyl 1.179 ethenyl H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 1.180 ethenyl H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- phenyl 1.181 1-butyl H 2-propyl S Me Me —CH₂— phenyl 1.182 1-butyl H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 1.183 1-butyl H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- phenyl 1.184 2-butyl H 2-propyl S Me Me —CH₂— phenyl 1.185 2-butyl H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 1.186 2-butyl H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- phenyl 1.187 CH₃SO₂— H 2-propyl S Me Me —CH₂— phenyl CH₂— 1.188 CH₃SO₂— H 2-propyl S Me Me —CH₂— 4-Cl-phenyl CH₂— 1.189 CH₃SO₂— H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- CH₂— phenyl 1.190 CH₃OOC— H 2-propyl S Me Me —CH₂— phenyl CH₂— 1.191 CH₃OOC— H 2-propyl S Me Me —CH₂— 4-Cl-phenyl CH₂— 1.192 CH₃OOC— H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- CH₂— phenyl 1.193 cyclo- H 2-propyl S Me Me —CH₂— phenyl hexyl 1.194 cyclo- H 2-propyl S Me Me —CH₂— 4-Cl-phenyl hexyl 1.195 cyclo- H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- hexyl phenyl 1.196 cyclo- H 2-propyl S Me Me —CH₂— phenyl pentyl 1.197 cyclo- H 2-propyl S Me Me —CH₂— 4-Cl-phenyl pentyl 1.198 cyclo- H 2-propyl S Me Me —CH₂— 3,5-di-CF₃- pentyl phenyl 1.199 Et H 2-propyl S H Me —CH₂— 2-MeO-5- MeOOC-phenyl 1.200 isopropyl H 2-propyl S H Me —CH₂— phenyl 1.201 isopropyl H 2-propyl S H Me —CH₂— 4-Cl-phenyl 1.202 isopropyl H 2-propyl S H Me —CH₂— 4-F-phenyl 1.203 propyl H 2-propyl S H Me —CH₂— phenyl 1.204 propyl H 2-propyl S H Me —CH₂— 4-Cl-phenyl 131-133 1.205 propyl H 2-propyl S H Me —CH₂— 4-F-phenyl 1.206 3-Cl- H 2-propyl S H Me —CH₂— phenyl propyl 1.207 3-Cl- H 2-propyl S H Me —CH₂— 4-Cl-phenyl 161-163 propyl 1.208 3-Cl- H 2-propyl S H Me —CH₂— 4-F-phenyl propyl 1.209 CF₃ H 2-propyl S H Me —CH₂— phenyl 1.210 CF₃ H 2-propyl S H Me —CH₂— 4-Cl-phenyl resin 1.211 CF₃ H 2-propyl S H Me —CH₂— 4-F-phenyl 1.212 CF₃CH₂ H 2-propyl S H Me —CH₂— phenyl 1.213 CF₃CH₂ H 2-propyl S H Me —CH₂— 4-Cl-phenyl 1.214 CF₃CH₂ H 2-propyl S H Me —CH₂— 4-F-phenyl 1.215 MeHN H 2-propyl S H Me —CH₂— phenyl 1.216 MeHN H 2-propyl S H Me —CH₂— 4-Cl-phenyl 1.217 MeHN H 2-propyl S H Me —CH₂— 4-F-phenyl 1.218 ethenyl H 2-propyl S H Me —CH₂— phenyl 1.219 ethenyl H 2-propyl S H Me —CH₂— 4-Cl-phenyl 136-137 1.220 ethenyl H 2-propyl S H Me —CH₂— 4-F-phenyl 1.221 1-butyl H 2-propyl S H Me —CH₂— phenyl 1.222 1-butyl H 2-propyl S H Me —CH₂— 4-Cl-phenyl 1.223 1-butyl H 2-propyl S H Me —CH₂— 4-F-phenyl 1.224 2-butyl H 2-propyl S H Me —CH₂— phenyl 1.225 2-butyl H 2-propyl S H Me —CH₂— 4-Cl-phenyl 1.226 2-butyl H 2-propyl S H Me —CH₂— 4-F-phenyl 1.227 CH₃SO₂— H 2-propyl S H Me —CH₂— phenyl CH₂— 1.228 CH₃SO₂— H 2-propyl S H Me —CH₂— 4-Cl-phenyl CH₂— 1.229 CH₃SO₂— H 2-propyl S H Me —CH₂— 4-F-phenyl CH₂— 1.230 CH₃OOC— H 2-propyl S H Me —CH₂— phenyl CH₂— 1.231 CH₃OOC— H 2-propyl S H Me —CH₂— 4-Cl-phenyl CH₂— 1.232 CH₃OOC— H 2-propyl S H Me —CH₂— 4-F-phenyl CH₂— 1.233 cyclo- H 2-propyl S H Me —CH₂— phenyl hexyl 1.234 cyclo- H 2-propyl S H Me —CH₂— 4-Cl-phenyl hexyl 1.235 cyclo- H 2-propyl S H Me —CH₂— 4-F-phenyl hexyl 1.236 cyclo- H 2-propyl S H Me —CH₂— phenyl pentyl 1.237 cyclo- H 2-propyl S H Me —CH₂— 4-Cl-phenyl pentyl 1.238 cyclo- H 2-propyl S H Me —CH₂— 4-F-phenyl pentyl 1.239 Me H 2-propyl S Me Me —CH₂— phenyl 1.240 Me H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 1.241 Me H 2-propyl S Me Me —CH₂— 4-F-phenyl 1.242 Et H 2-propyl S Me Me —CH₂— phenyl 1.243 Et H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 153-155 1.244 Et H 2-propyl S Me Me —CH₂— 4-F-phenyl 1.245 Me₂N H 2-propyl S Me Me —CH₂— phenyl 1.246 Me₂N H 2-propyl S Me Me —CH₂— 4-Cl-phenyl 1.247 Me₂N H 2-propyl S Me Me —CH₂— 4-F-phenyl 1.248 Et H 1-propyl S H Me —CH₂— phenyl 1.249 Et H 1-propyl S H Me —CH₂— 4-Cl-phenyl 117-122 1.250 Et H 1-propyl S H Me —CH₂— 4-F-phenyl 1.251 1-pyrroli- H 2-propyl S H Me —CH₂— phenyl dinyl 1.252 1-pyrroli- H 2-propyl S H Me —CH₂— 4-Cl-phenyl resin dinyl 1.253 1-pyrroli- H 2-propyl S H Me —CH₂— 4-F-phenyl dinyl 1.254 Me H 2-propyl S H Me —CH₂— 4-Me-phenyl 1.255 Et H 2-propyl S H Me —CH₂— 4-Me-phenyl 103-105 1.256 Me₂N H 2-propyl S H Me —CH₂— 4-Me-phenyl 1.257 Me H 2-propyl S H Me —CH₂— 2-CH₃OOC- phenyl 1.258 Et H 2-propyl S H Me —CH₂— 2-CH₃OOC- 70-73 phenyl 1.259 Me₂N H 2-propyl S H Me —CH₂— 2-CH₃OOC- phenyl 1.260 Me H 2-propyl S H Me —CH₂— 2,4-di-F-phenyl 1.261 Et H 2-propyl S H Me —CH₂— 2,4-di-F-phenyl 113-114 1.262 Me₂N H 2-propyl S H Me —CH₂— 2,4-di-F-phenyl 1.263 Me H 2-propyl S H Me —CH₂— 1-naphthyl 1.264 Et H 2-propyl S H Me —CH₂— 1-naphthyl  98-100 1.265 Me₂N H 2-propyl S H Me —CH₂— 1-naphthyl 1.266 Me H 2-propyl S H Me —CH₂— 4-F-3-Cl-phenyl 1.267 Et H 2-propyl S H Me —CH₂— 4-F-3-Cl-phenyl 102-104 1.268 Me₂N H 2-propyl S H Me —CH₂— 4-F-3-Cl-phenyl 1.269 Me H 2-propyl S H Me —CH₂— 1-butyl resin 1.270 Et H 2-propyl S H Me —CH₂— 1-butyl oil 1.271 Me₂N H 2-propyl S H Me —CH₂— 1-butyl 94-95 1.272 Me H 2-propyl S H Me —CH₂— 2-CH₃-2-propyl 1.273 Et H 2-propyl S H Me —CH₂— 2-CH₃-2-propyl 1.274 Me₂N H 2-propyl S H Me —CH₂— 2-CH₃-2-propyl 1.275 Me H 2-propyl S H Me —CH₂— cyclopentyl 1.276 Et H 2-propyl S H Me —CH₂— cyclopentyl 1.277 Me₂N H 2-propyl S H Me —CH₂— cyclopentyl 1.278 Me H 2-propyl S H Me —CH₂— cyclohexyl 1.279 Et H 2-propyl S H Me —CH₂— cyclohexyl 1.280 Me₂N H 2-propyl S H Me —CH₂— cyclohexyl 1.281 Me H 2-propyl S H Me —CH₂— 3-F-4-Me-phenyl 1.282 Et H 2-propyl S H Me —CH₂— 3-F-4-Me-phenyl 128-131 1.283 Me₂N H 2-propyl S H Me —CH₂— 3-F-4-Me-phenyl 1.284 Me₂N H 2-propyl S H Me —CH₂— 4-F-phenyl 131-133 1.285 Me H 2-propyl S H Me —CH₂— 4-F-phenyl 136-138

Example 2.001

(S)-2-(Propylsulfonyl-amino)-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(4-chlorophenyl)-2-propyn-1-yloxy)-phenyl}-ethyl]-amide

a) 32.9 g of BOC-L-valine and 16.7 ml of N-methylmorpholine are dissolved in 350 ml of tetrahydrofuran and cooled to −20° C. 19.8 ml of isobutyl chloroformate are added dropwise to that solution over a period of 15 minutes. The mixture is stirred for 30 minutes, during which time the temperature rises to −7° C. The mixture is then cooled to −20° C., and 35.4 g of 2-(4-benzyloxy-3-methoxy-phenyl)-ethylamine in 50 ml of tetrahydrofuran are added dropwise over a period of 10 minutes. The reaction mixture is stirred for 30 minutes at −20° C. and then for 4 hours at room temperature. It is introduced into 300 ml of 1N hydrochloric acid. Extraction is carried out twice using 400 ml of ethyl acetate each time. The organic phases are washed once with 300 ml of 1N hydrochloric acid and once with 300 ml of saturated sodium chloride solution, dried over magnesium chloride and concentrated, yielding (S)-2-(tert-butoxycarbonyl-amino)-3-methyl-butyric acid N-[2-(4-benzyloxy-3-methoxy-phenyl)-ethyl]-amide, which is recrystallised from ethyl acetate/n-hexane, m.p. 115-118° C.

b) 50.4 g of (S)-2-(tert-butoxycarbonyl-amino)-3-methyl-butyric acid N-[2-(4-benzyloxy-3-methoxy-phenyl)-ethyl]-amide are dissolved in 1000 ml of tetrahydrofuran and hydrogenated with hydrogen for 2 hours over 10 g of 10% palladium on activated carbon under normal pressure and at room temperature. Filtration with suction is carried out over Celite. The filtrate is concentrated by evaporation, yielding (S)-2-(tert-butoxycarbonyl-amino)-3-methyl-butyric acid N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-amide in the form of an oil.

c) 40.4 g of (S)-2-(tert-butoxycarbonyl-amino)-3-methyl-butyric acid N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-amide, 53.0 g of toluene-4-sulfonic acid [3-(4-chlorophenyl)-2-propyn-1-yl] ester (Example 5.005) and 180 ml of 1M sodium methanolate solution in methanol are heated at reflux for 3 hours in 1000 ml of methanol. The reaction mixture is concentrated to about a third of the volume and introduced into 500 ml of ethyl acetate. Extraction is carried out twice using 300 ml of saturated sodium chloride solution each time. The organic phase is dried over magnesium sulfate and concentrated, yielding (S)-2-(butoxycarbonyl-amino)-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(4-chlorophenyl)-2-propyn-1-yloxy)-phenyl}-ethyl]-amide, which is recrystallised from ethyl acetate/n-hexane, m.p. 141-142° C.

d) 5.8 g of (S)-2-(butoxycarbonyl-amino)-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(4-chlorophenyl)-2-propyn-1-yloxy)-phenyl}-ethyl]-amide and 5 g of concentrated hydrochloric acid are stirred for 10 minutes in a mixture of 20 ml of diethyl ether and 20 ml of dichloromethane at 0° C. Stirring is continued overnight at room temperature. The reaction mixture is introduced into 100 ml of 2N hydrochloric acid and extraction is carried out twice using 150 ml of diethyl ether each time. The aqueous phase is adjusted to pH 11 with 5M sodium hydroxide. Extraction is then carried out twice using 150 ml of ethyl acetate each time. The organic phases are washed twice with 50 ml of saturated sodium chloride solution each time, dried over sodium sulfate and concentrated, yielding (S)-2-amino-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(4-chlorophenyl)-2-propyn-1-yloxy)-phenyl}-ethyl]-amide, which is recrystallised from ethyl acetate/n-hexane, m.p. 115-117° C.

e) 1.5 g of (S)-2-amino-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(4-chlorophenyl)-2-propyn-1-yloxy)-phenyl}-ethyl]-amide and 0.5 ml of triethylamine are dissolved in 50 ml of dioxane. 0.4 ml of 1-propanesulfonyl chloride is added, and the reaction mixture is stirred overnight at room temperature. It is introduced into 200 ml of saturated sodium chloride solution. Extraction is carried out twice using 150 ml of ethyl acetate each time. The organic phases are washed once with 100 ml of saturated sodium chloride solution, dried over magnesium sulfate and concentrated, yielding (S)-2-(propylsulfonyl-amino)-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(4-chlorophenyl)-2-propyn-1-yloxy)-phenyl}-ethyl]-amide, which is chromatographed on silica gel with ethyl acetate/n-hexane (1:1) and recrystallised from ethyl acetate/n-hexane, m.p. 131-133° C.

The Examples listed in Table 2 are prepared in an analogous manner.

TABLE 2

Comp. Conf. Phys. data Identical to No. R₁ n R₂ α-C B m.p. ° C. Comp. No. 2.001 2-propyl 1 2-propyl S 4-Cl-phenyl 131-133 1.204 2.002 ethenyl 1 2-propyl S 4-Cl-phenyl 136-137 1.219 2.003 CF₃ 1 2-propyl S 4-Cl-phenyl resin 1.210 2.004 3-chloro- 1 2-propyl S 4-Cl-phenyl 161-163 1.207 propyl 2.005 1-pyrroli- 1 2-propyl S 4-Cl-phenyl resin 1.252 dinyl 2.006 ethyl 0 2-propyl S 4-Cl-phenyl 130-134 2.007 2-propyl 0 2-propyl S 4-F-phenyl resin 2.008 cyclo- 0 2-propyl S 4-F-phenyl resin hexyl

Example 3.001

(S)-2-(Ethylsulfonyl-amino)-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(2-thienyl)-2-propyn-1-yloxy)-phenyl}-ethyl]-amide

2 g of (S)-2-(ethylsulfonyl-amino)-3-methyl-butyric acid N-[2-(3-methoxy-4-propargyloxy-phenyl)-ethyl]-amide, 2.1 g of 2-iodothiophene and 2 ml of triethylamine are heated to 40° C. in 50 ml of chloroform. 70 mg of bis(triphenylphosphine)palladium(II) chloride and 32 mg of copper(I) iodide are added thereto. The reaction mixture is stirred for one hour at 60° C.

Concentration to dryness by evaporation is carried out. The residue is chromatographed on silica gel with ethyl acetate/n-hexane (2:1) and the resulting substance, (S)-2-(ethylsulfonylamino)-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(2-thienyl)-2-propyn-1-yloxy)-phenyl}-ethyl]-amide, is recrystallised from ethyl acetate/n-hexane, m.p. 154-155° C. (identical to comp. no. 1.105).

The Examples listed in Table 3 are prepared in an analogous manner.

TABLE 3

Comp. Conf. Phys. data Identical to No. R₁ n R₂ α-C B m.p. ° C. Comp. No. 3.001 ethyl 1 2-propyl S 2-thienyl 154-155 1.105 3.002 ethyl 1 2-propyl S 4-MeO-phenyl 72-75 1.037

Example 4.001

(S)-2-(Cyclohexylsulfonyl-amino)-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(4-fluorophenyl)-2-propyn-1-vioxy)-phenyl}-ethyl]-amide (Process b))

A saturated solution of potassium permanganate in acetone is added dropwise, at room temperature, to 0.9 g of (S)-2-(cyclohexylsulfinyl-amino)-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(4-fluorophenyl)-2-propyn-1-yloxy)-phenyl}-ethyl]-amide (comp. 2.008) in 25 ml of acetone until a permanent violet colouration of the reaction mixture is observed.

Filtration is carried out over kieselguhr, followed by washing with acetone. The filtrate is concentrated to dryness, yielding (S)-2-(cyclohexylsulfonyl-amino)-3-methyl-butyric acid N-[2-{3-methoxy-4-(3-(4-fluorophenyl)-2-propyn-1-yloxy)-phenyl}-ethyl]-amide (identical to comp. 1.235) in the form of a resin, which is purified by chromatography on silica gel with ethyl acetate/n-hexane.

PREPARATION EXAMPLE FOR INTERMEDIATES: Example 5.001

Toluene-4-sulfonic acid (3-phenyl-2-propyn-1-yl) ester

25 g of 3-phenyl-2-propyn-1-ol and 40 g of toluene-4-sulfonic acid chloride are dissolved in 500 ml of diethyl ether and cooled to −20° C. 26.6 g of finely powdered potassium hydroxide are added in portions to that solution, over a period of 20 minutes, in such a manner that the internal temperature of the reaction mixture does not exceed −5° C. When the addition is complete, the reaction mixture is stirred for 2 hours at from 0 to 5° C. and then introduced into one litre of ice-water. Extraction is carried out twice using one litre of diethyl ether each time. The organic phases are washed once with 500 ml of saturated sodium chloride solution, combined, dried over sodium sulfate and concentrated, yielding toluene-4-sulfonic acid (3-phenyl-2-propyn-1-yl) ester in the form of a colourless resin.

The Examples given in Table 5 are obtained analogously to the above Example.

TABLE 5

Comp. Phys. No. A B data 5.001 —CH₂— phenyl resin 5.002 —CH(CH₃)— phenyl 5.003 —C(CH₃)₂— phenyl 5.004 —CH₂— 4-F-phenyl 71-72 5.005 —CH₂— 4-Cl-phenyl oil 5.006 —CH₂— 4-Br-phenyl 68-69 5.007 —CH₂— 4-MeO-phenyl 5.008 —CH₂— 4-NO₂-phenyl 109-112 5.009 —CH₂— 4- MeOOC-phenyl 75-77 5.010 —CH₂— 4-CF₃-phenyl 80-81 5.011 —CH₂— 4CF₃O-phenyl 5.012 —CH₂— 4-CH₃CO-phenyl 84-86 5.013 —CH₂— 4-CN-phenyl 5.014 —CH₂— 4-(tert-butyl)-phenyl 5.015 —CH₂— 4-ethyl-phenyl 5.016 —CH₂— 4-CHF₂O-phenyl 5.017 —CH₂— 4-PhCO-phenyl 5.018 —CH₂— 4-NH₂-phenyl 5.019 —CH₂— 4-MeS-phenyl 5.020 —CH₂— 3-Br-phenyl 59-61 5.021 —CH₂— 3-F-phenyl 42-43 5.022 —CH₂— 3-Cl-phenyl 60-62 5.023 —CH₂— 3-MeO-phenyl 58-59 5.024 —CH₂— 3-CF₃-phenyl oil 5.025 —CH₂— 3-MeO-phenyl 65-66 5.026 —CH₂— 3-NO₂-phenyl 98-99 5.027 —CH₂— 3-NH₂-phenyl 5.028 —CH₂— 3-EtOOC-phenyl 5.029 —CH₂— 3-MeOOC-phenyl 5.030 —CH₂— 3-CN-phenyl 5.031 —CH₂— 2-Br-phenyl 72-73 5.032 —CH₂— 2-F-phenyl 5.033 —CH₂— 2-Cl-phenyl 82-85 5.034 —CH₂— 2-MeO-phenyl 5.035 —CH₂— 2-CF₃-phenyl 40-42 5.036 —CH₂— 2-Me-phenyl 75-77 5.037 —CH₂— 2-NO₂-phenyl 5.038 —CH₂— 2-CF₃O-phenyl 5.039 —CH₂— 2-MeS-phenyl 5.040 —CH₂— 3,4-di-F-phenyl oil 5.041 —CH₂— 3,4-d-Cl-phenyl 63-65 5.042 —CH₂— 3,4-di-Me-phenyl 74-77 5.043 —CH₂— 3-F-4-Me-phenyl 5.044 —CH₂— 3-Me-4-F-phenyl 5.045 —CH₂— 3-Cl-4-Me-phenyl 62-64 5.046 —CH₂— 3-F-4-Cl-phenyl oil 5.047 —CH₂— 3-F-4-Br-phenyl 5.048 —CH₂— 3-Me-4-Br-phenyl 5.049 —CH₂— 3-Me-4-F-phenyl 5.050 —CH₂— 2,4-di-Cl-phenyl 91-92 5.051 —CH₂— 2-F-4-Br-phenyl 5.052 —CH₂— 2,4-di-Me-phenyl 55-57 5.053 —CH₂— 2-Cl-4-CF₃-phenyl 5.054 —CH₂— 2-CF₃-4-Cl-phenyl 5.055 —CH₂— 2,4-di-MeO-phenyl 5.056 —CH₂— 2,5-di-Cl-phenyl 90-91 5.057 —CH₂— 2-Cl-5-CF₃-phenyl 76-77 5.058 —CH₂— 2,5-di-Me-phenyl 5.059 —CH₂— 2-MeO-5-Cl-phenyl 5.060 —CH₂— 2-MeO-5-MeOOC-phenyl 5.061 —CH₂— 2-Me-5-Cl-phenyl 5.062 —CH₂— 3,5-di-Cl-phenyl 64-66 5.063 —CH₂— 3-F-5-NO₂-phenyl 5.064 —CH₂— 3,5-di-CF₃-phenyl oil 5.065 —CH₂— 3,5-di-Me-phenyl 5.066 —CH₂— 2,4,5-tri-Cl-phenyl 95-96 5.067 —CH₂— 2,3,4,5,6-penta-F-phenyl 5.068 —CH₂— 2-pyridyl 5.069 —CH₂— 6-Me-2-pyridyl 5.070 —CH₂— 3-Cl-5-CF₃-2-pyridyl 5.071 —CH₂— 5-CF₃-pyridyl 5.072 —CH₂— 3-pyridyl 5.073 —CH₂— 4-pyridyl 5.074 —CH₂— 2-pyrimidinyl 5.075 —CH₂— 4-pyrazolyl 5.076 —CH₂— 2-thienyl 5.077 —CH₂— 5-Me-2-thienyl 5.078 —CH₂— 2,4,5-tri-Me-thienyl 5.079 —CH₂— 2-benzothiazolyl 5.080 —CH₂— 2-quinolinyl 5.081 —CH₂— 2-Me-phenyl 55-57 5.082 —CH₂— 2-MeOOC-phenyl 59-61 5.083 —CH₂— 2,4-di-F-phenyl oil 5.084 —CH₂— 1-naphthyl oil 5.085 —CH₂— 4-F-3-Me-phenyl 38-40 5.086 —CH₂— 3-Cl-4-F-phenyl 53-55 5.087 —CH₂— butyl oil

Example 6.001

3-(4-chloro-phenyl)-2-propyn-1-ol

A mixture of 6 g of 1-chloro-4-iodo-benzene, 1.8 ml of propargyl alcohol and 5.2 ml of triethylamine in 30 ml of chloroform is placed under a nitrogen atmosphere. 208 mg of bis(triphenylphosphine)palladium(II) dichloride and 98 mg of copper(I) iodide are added thereto. The reaction mixture is stirred for one hour at 40° C. 300 ml of hot n-hexane are then added. The n-hexane phase is decanted off. The residue is again digested with 200 ml of hot n-hexane, and the n-hexane phase is decanted off. The n-hexane phases are concentrated and the residue is subjected to flash chromatography on silica gel with ethyl acetate/n-hexane (1:4), yielding 3-(4-chloro-phenyl)-2-propyn-1-ol, which can be recrystallised from n-hexane, m.p. 78-80° C.

The Examples given in Table 6 are obtained analogously to the above Example.

TABLE 6

Comp. Phys. data No. A B m.p. ° C. 6.001 —CH₂— 4-Cl-phenyl 78-80 6.002 —CH(CH₃)— phenyl 6.003 —C(CH₃)₂— phenyl 6.004 —CH₂— 4-F-phenyl oil 6.005 —CH₂— 4-Br-phenyl 80-81 6.006 —CH₂— 4-MeO-phenyl 6.007 —CH₂— 4-NO₂-phenyl 95-97 6.008 —CH₂— 4-MeOOC-phenyl 73-75 6.009 —CH₂— 4-CF₃-phenyl 40-41 6.010 —CH₂— 4-CF₃O-phenyl 6.011 —CH₂— 4-CH₃CO-phenyl 77-80 6.012 —CH₂— 4-CN-phenyl 6.013 —CH₂— 4-(tert-butyl)-phenyl 6.014 —CH₂— 4-ethyl-phenyl 6.015 —CH₂— 4-CHF₂O-phenyl 6.016 —CH₂— 4-PhCO-phenyl 6.017 —CH₂— 4-NH₂-phenyl 6.018 —CH₂— 4-MeS-phenyl 6.019 —CH₂— 3-Br-phenyl 24-27 6.020 —CH₂— 3-F-phenyl oil 6.021 —CH₂— 3-Cl-phenyl oil 6.022 —CH₂— 3-MeO-phenyl oil 6.023 —CH₂— 3-CF₃-phenyl oil 6.024 —CH₂— 3-Me-phenyl oil 6.025 —CH₂— 3-NO₂-phenyl oil 6.026 —CH₂— 3-NH₂-phenyl 6.027 —CH₂— 3-EtOOC-phenyl 6.028 —CH₂— 3-MeOOC-phenyl 6.029 —CH₂— 3-CN-phenyl 6.030 —CH₂— 2-Br-phenyl oil 6.031 —CH₂— 2-F-phenyl 6.032 —CH₂— 2-Cl-phenyl oil 6.033 —CH₂— 2-MeO-phenyl 6.034 —CH₂— 2-CF₃-phenyl oil 6.035 —CH₂— 2-Me-phenyl oil 6.036 —CH₂— 2-NO₂-phenyl 6.037 —CH₂— 2-CF₃O-phenyl 6.038 —CH₂— 2-MeS-phenyl 6.039 —CH₂— 3,4-di-F-phenyl oil 6.040 —CH₂— 3,4-di-Cl-phenyl 62-63 6.041 —CH₂— 3,4-di-Me-phenyl oil 6.042 —CH₂— 3-F-4-Me-phenyl 6.043 —CH₂— 3-Me-4-F-phenyl 6.044 —CH₂— 3-Cl-4-Me-phenyl 25-27 6.045 —CH₂— 3-F-4-Cl-phenyl 38-41 6.046 —CH₂— 3-F-4-Br-phenyl 6.047 —CH₂— 3-Me-4-Br-phenyl 6.048 —CH₂— 3-Me-4-F-phenyl 6.049 —CH₂— 2,4-di-Cl-phenyl 79-81 6.050 —CH₂— 2-F-4-Br-phenyl 6.051 —CH₂— 2,4-di-Me-phenyl oil 6.052 —CH₂— 2-Cl-4-CF₃-phenyl 6.053 —CH₂— 2-CF₃-4-Cl-phenyl 6.054 —CH₂— 2,4-di-MeO-phenyl 6.055 —CH₂— 2,5-di-Cl-phenyl 81-82 6.056 —CH₂— 2-Cl-5-CF₃-phenyl oil 6.057 —CH₂— 2,5-di-Me-phenyl 6.058 —CH₂— 2-MeO-5-Cl-phenyl 6.059 —CH₂— 2-MeO-5-MeOOC-phenyl 6.060 —CH₂— 2-Me-5-Cl-phenyl 6.061 —CH₂— 3,5-di-Cl-phenyl 65-67 6.062 —CH₂— 3-F-5-NO₂-phenyl 6.063 —CH₂— 3,5-di-Me-phenyl 6.064 —CH₂— 2,4,5-tri-Cl-phenyl 127-130 6.065 —CH₂— 2,3,4-5,6-penta-F-phenyl 6.066 —CH₂— 2-pyridyl 6.067 —CH₂— 6-Me-2-pyridyl 6.068 —CH₂— 3-Cl-5-CF₃-2-pyridyl 6.069 —CH₂— 5-CF₃-pyridyl 6.070 —CH₂— 3-pyridyl 6.071 —CH₂— 4-pyridyl 6.072 —CH₂— 2-pyrimidinyl 6.073 —CH₂— 4-pyrazolyl 6.074 —CH₂— 2-thienyl 6.075 —CH₂— 5-Me-2-thienyl 6.076 —CH₂— 2,4,5-tri-Me-thienyl 6.077 —CH₂— 2-benzothiazolyl 6.078 —CH₂— 2-quinolinyl 6.079 —CH₂— 4-Me-phenyl oil 6.080 —CH₂— 2-MeOOC-phenyl oil 6.081 —CH₂— 2,4-di-F-phenyl oil 6.082 —CH₂— 1-naphthyl oil 6.083 —CH₂— 4-F-3-Me-phenyl 27-30 6.084 —CH₂— 3-Cl-4-F-phenyl 29-32

Formulations may be prepared analogously to those described in, for example, WO 95/30651.

BIOLOGICAL EXAMPLES B-1: Action Against Plasmoedara Viticola on Vines

a) Residual-protective Action

Vine seedlings are sprayed at the 4- to 5-leaf stage with a spray mixture (0.02% active ingredient) prepared from a wettable powder formulation of the test compound. After 24 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation for 6 days at 95-100% relative humidity and 20° C.

b) Residual-curative Action

Vine seedlings are infected at the 4- to 1leaf stage with a sporangia suspension of the fungus. After incubation for 24 hours in a humidity chamber at 95-100% relative humidity and 20° C., the infected plants are dried and sprayed with a spray mixture (0.02% active ingredient) prepared from a wettable powder formulation of the test compound. After the spray coating has dried, the treated plants are placed in the humidity chamber again. Fungus infestation is evaluated 6 days after infection.

Compounds of Table 1 exhibit a very good fungicidal action against Plasmopara viticola on vines. Compounds nos. 1.001, 1.003, 1.010, 1.033, 1.034, 1.035, 1.036, 1.037. 1.038, 1.039, 1.040, 1.042, 1.050, 1.051, 1.052, 1.053, 1.054, 1.055, 1.056, 1.061, 1.063, 1.065, 1.066, 1.070, 1.071, 1.072, 1.073, 1.075, 1.076, 1.080, 1.082, 1.086, 1.087, 1.091, 1.093, 1.095, 1.105, 1.128, 1.129, 1.136, 1.204, 1.207, 1.210, 1.219, 1.243, 1.249, 1.255, 1.258, 1.261, 1.264, 1.267, 1.270, 1.271, 1.282, 1.284 and 1.285, inter alia, achieve complete suppression of fungus infestation (residual infestation 0 to 5%). On the other hand, Plasmopara infestation on untreated and infected control plants is 100%.

B-2: Action Against Phytophthora on Tomato Plants

a) Residual-protective Action

After a cultivation period of 3 weeks, tomato plants are sprayed with a spray mixture (0.02% active ingredient) prepared from a wettable powder formulation of the test compound. After 48 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 5 days at 90-100% relative humidity and 20° C.

b) Systemic Action

After a cultivation period of 3 weeks, tomato plants are watered with a spray mixture (0.02% active ingredient based on the volume of the soil) prepared from a wettable powder formulation of the test compound. Care is taken that the spray mixture does not come into contact with the parts of the plants that are above the ground. After 96 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 4 days at 90-100% relative humidity and 20° C.

Compounds of Table 1 exhibit a lasting effect (less than 20% fungus infestation). Infestation is prevented virtually completely (0 to 5% infestation) with compounds nos. 1.001, 1.003, 1.010, 1.033, 1.034, 1.035, 1.036, 1.037, 1.038, 1.039, 1.040, 1.042, 1.050, 1.051, 1.052, 1.053, 1.054, 1.055, 1.056, 1.061, 1.063, 1.065, 1.066, 1.070, 1.071, 1.072, 1.073, 1.075, 1.076, 1.080, 1.082, 1.086, 1.087, 1.091, 1.093, 1.095, 1.105, 1.128, 1.129, 1.136, 1.204, 1.207, 1.210, 1.219, 1.243, 1.249, 1.255, 1.258, 1.261, 1.264, 1.267, 1.270, 1.271, 1.282, 1.284 and 1.285. On the other hand, Phytophthora infestation on untreated and infected control plants is 100%.

B-3: Action against Phytophthora on Potato Plants

a) Residual-protective Action

2-3 week old potato plants (Bintje variety) are sprayed with a spray mixture (0.02% active ingredient) prepared from a wettable powder formulation of the test compound. After 48 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 4 days at 90-100% relative humidity and 20° C.

b) Systemic Action

2-3 week old potato plants (Bintje variety) are watered with a spray mixture (0.02% active ingredient based on the volume of the soil) prepared from a wettable powder formulation of the test compound. Care is taken that the spray mixture does not come into contact with the parts of the plants that are above the ground. After 48 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 4 days at 90-100% relative humidity and 20° C. Infestation is prevented virtually completely (0 to 5% infestation) with compounds of Table 1 (e.g. compounds nos. 1.001, 1.003, 1.010, 1.033, 1.034, 1.035, 1.036, 1.037, 1.038, 1.039, 1.040, 1.042, 1.050, 1.051, 1.052, 1.053, 1.054, 1.055, 1.056, 1.061, 1.063, 1.065, 1.066, 1.070, 1.071, 1.072, 1.073, 1.075, 1.076, 1.080, 1.082, 1.086, 1.087, 1.091, 1.093, 1.095, 1.105, 1.128, 1.129, 1.136, 1.204, 1.207, 1.210, 1.219, 1.243, 1.249, 1.255, 1.258, 1.261, 1.264, 1.267, 1.270, 1.271, 1.282, 1.284 and 1.285). On the other hand, Phytophthora infestation on untreated and infected control plants is 100%. 

What is claimed is:
 1. A compound of formula I

wherein n is a number zero or one; R₁ is C₁-C₁₂alkyl that is unsubstituted or may be substituted by C₁-C₄alkoxy, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, C₃-C₈cycloalkyl, cyano, C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl or by C₃-C₆alkynyloxycarbonyl; C₃-C₈cycloalkyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl; or a group NR₁₁R₁₂ wherein R₁₁ and R₁₂ are each independently of the other hydrogen or C₁-C₆alkyl, or together are tetra- or penta-methylene; R₂ and R₃ are each independently of the other hydrogen; C₁-C₈alkyl; C₁-C₈alkyl substituted by hydroxy, C₁-C₄alkoxy, mercapto or by C₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl; C₃-C₈cycloalkyl-C₁-C₄alkyl; or the two groups R₂ and R₃ together with the carbon atom to which they are bonded form a three- to eight-membered ring; R₄, R₅, R₆ and R₇ are identical or different and are each independently of the others hydrogen or C₁-C₄alkyl; R₈ is C₁-C₆alkyl, C₃-C₆alkenyl or C₃-C₈alkynyl; A is C₁-C₆alkylene; and B is optionally mono- or poly-nuclear, unsubstituted or substituted aryl; optionally mono- or poly-nuclear, unsubstituted or substituted heteroaryl; C₄-C₁₂alkyl; or C₃-C₈cycloalkyl.
 2. A compound according to claim 1 wherein R₁ is C₁-C₁₂alkyl; C₃-C₈cycloalkyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl; or a group NR₁₁R₁₂ wherein R₁₁ and R₁₂ are each independently of the other hydrogen or C₁-C₆alkyl, or together are tetra- or penta-methylene; R₂ is hydrogen; R₃ is C₁-C₈alkyl; C₁-C₈alkyl substituted by hydroxy, C₁-C₄alkoxy, mercapto or by C₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl; or C₃-C₈cycloalkyl-C₁-C₄alkyl; B is phenyl; naphthyl; or heteroaryl that is formed from one or two five- or six-membered rings and that may contain from 1 to 4 identical or different hetero atoms selected from nitrogen, oxygen and sulfur; wherein the phenyl, naphthyl or heteroaryl may optionally carry from 1 to 5 identical or different substituents selected from: C₁-C₈alkyl, C₂-C₈alkenyl, C₂-C₈-alkynyl, C₃-C₈cycloalkyl, C₃-C₈cycloalkyl-C₁-C₄alkyl, phenyl, phenyl-C₁-C₄alkyl, those groups being unsubstituted or mono- to per-halogenated and the halogen atoms being identical or different; C₁-C₈alkoxy; C₃-C₈alkenyloxy; C₃-C₈alkynyloxy; C₁-C₄alkoxy-C₁-C₄alkyl; C₁-C₈haloalkoxy; C₁-C₈alkylthio; C₁-C₈haloalkylthio; C₁-C₈alkylsulfonyl; formyl; C₂-C₈alkanoyl; hydroxy; halogen; cyano; nitro; amino; C₁-C₈alkylamino; C₁-C₈dialkylamino; carboxy; C₁-C₈alkoxycarbonyl; C₃-C₈alkenyloxycarbonyl; and C₃-C₈alkynyloxycarbonyl.
 3. A compound of formula I according to claim 2 wherein R₁ is C₁-C₆alkyl; C₅-C₆cycloalkyl; C₂-C₆alkenyl; C₁-C₆haloalkyl; or a group NR₁₁R₁₂ wherein R₁₁ and R₁₂ are each independently of the other hydrogen or C₁-C₆alkyl; R₃ is C₁-C₈alkyl; or C₃-C₆cycloalkyl; R₄ is hydrogen or C₁-C₄alkyl; R₅, R₆ and R₇ are hydrogen; R₈ is C₁-C₆alkyl; A is C₁-C₂alkylene; and B is phenyl, naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzothiazolyl or benzoxazolyl, each unsubstituted or substituted by from 1 to 5 substituents selected from: C₁-C₈alkyl, C₂-C₈alkenyl, C₂-C₈alkynyl, C₃-C₈cycloalkyl, C₃-C₈cycloalkyl-C₁-C₄alkyl, phenyl, phenyl-C₁-C₄alkyl, those groups being unsubstituted or mono- to per-halogenated and the halogen atoms being identical or different; C₁-C₈alkoxy; C₃-C₈alkenyloxy; C₃-C₈alkynyloxy; C₁-C₄alkoxy-C₁-C₄alkyl; C₁-C₈haloalkoxy; C₁-C₈alkylthio; C₁-C₈haloalkylthio; C₁-C₈alkylsulfonyl; formyl; C₂-C₈alkanoyl; hydroxy; halogen; cyano; nitro; amino; C₁-C₈alkylamino; C₁-C₈dialkylamino; carboxy; C₁-C₈alkoxycarbonyl; C₃-C₈alkenyloxycarbonyl; and C₃-C₈alkynyloxycarbonyl.
 4. A compound of formula I according to claim 3 wherein n is the number one; R₁ is C₁-C₆alkyl; C₁-C₆haloalkyl; or a group NR₁₁R₁₂ wherein R₁₁ and R₁₂ are each independently of the other C₁-C₄alkyl; R₃ is C₃-C₄alkyl; or cyclopropyl; R₄ is hydrogen or methyl; R₈ is C₁-C₂alkyl; A is methylene; and B is phenyl, naphthyl, turyl, thienyl, pyridyl, pyrimidinyl, triazinyl, benzothiophenyl, each unsubstituted or substituted by from 1 to 3 substituents selected from: C₁-C₈alkyl, phenyl, those groups being unsubstituted or mono- to per-halogenated and the halogen atoms being identical or different; C₁-C₈alkoxy; C₃-C₈alkenyloxy; C₃-C₈alkynyloxy; C₁-C₈haloalkoxy; C₁-C₈alkylthio; C₁-C₈haloalkylthio; C₁-C₈alkylsulfonyl; formyl; C₁-C₈alkanoyl; hydroxy; halogen; cyano; nitro; and C₁-C₈alkoxycarbonyl.
 5. A compound of formula I according to claim 4 wherein R₁ is C₁-C₄alkyl; or dimethylamino; R₃ is 2-propyl; R₈ is methyl; B is phenyl, naphthyl, each unsubstituted or substituted by from 1 to 3 substituents selected from: C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio, C₁-C₈haloalkylthio, halogen, cyano, nitro and C₁-C₈alkoxycarbonyl.
 6. A compound of formula I according to claim 4 wherein R₁ is C₁-C₄alkyl; or dimethylamino; R₃ is 2-propyl; R₈ is methyl; B is thienyl, pyridyl, each unsubstituted or substituted by from 1 to 3 substituents selected from: C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio, C₁-C₈haloalkylthio, halogen, cyano, nitro and C₁-C₈alkoxycarbonyl.
 7. A process for the preparation of a compound of formula I according to claim 1, which comprises a) reacting a substituted amino acid of formula II

 wherein the radicals R₁, R₂ and R₃ and n are as defined above, or a carboxy-activated derivative thereof, if desired in the presence of a catalyst, if desired in the presence of an acid-binding agent and if desired in the presence of a diluent, at temperatures of from −80 to +150° C., with an amine of formula III

 wherein R₄, R₅, R₆, R₇, R₈, A and B are as defined above; or b) oxidising a compound of formula I′

 wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, A and B are as defined above, with the proviso that none of the substituents R₁, R₂, R₃ and B contains a thiol or alkylthio group, with an oxidising agent, in an inert diluent, if desired in the presence of an acid or if desired in the presence of a base, at temperatures of from −80 to +150° C.; or c) reacting a compound of formula IV

 wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇ and R₈ and n are as defined above, with a compound of formula V Y—A—≡—B  V, wherein A and B are as defined above and wherein Y is a leaving group, in an inert diluent, if desired in the presence of an acid-binding agent, at temperatures of from −80 to +200° C.; or d) reacting a sulfonic acid or sulfinic acid, or a sulfonic acid or sulfinic acid derivative, of formula VI

 wherein R₁ and n are as defined above and wherein X is an OH group or a leaving group, respectively, with an amine of formula VII

 wherein R₂, R₃, R₄, R₅, R₆, R₇, R₈, A and B are as defined above, in an inert diluent, if desired in the presence of an acid-binding agent, at temperatures of from −80 to +150° C.; or e) reacting an alkyne of formula I″

 wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, A and n are as defined above, with an aryl or heteroaryl halide in an inert diluent, if desired in the presence of an acid-binding agent, if desired in the presence of one or more transition metal salts and if desired in the presence of one or more transition metal complexes or transition metal complex salts, at temperatures of from −80 to +200° C.
 8. A composition for controlling and protecting against phytopathogenic microorganisms, comprising a compound according to claim 1 as active ingredient together with a suitable carrier.
 9. A composition according to claim 8 comprising a compound of formula I according to claim 2 as active ingredient.
 10. A method of controlling and preventing an infestation of crop plants by phytopathogenic microorganisms, which comprises the application of a compound of formula I according to claim 1 as active ingredient to the plant, to parts of plants or to the locus thereof.
 11. A method according to claim 10, wherein a compound of formula I according to claim 2 is applied as active ingredient.
 12. A method according to claim 10, wherein the phytopathogenic microorganisms are fungal organisms.
 13. A compound of formula III

wherein R₄, R₅, R₆, R₇, R₈, A and B are as defined above.
 14. A process for the preparation of a compound of formula III according to claim 13, which comprises using

wherein Step A is the alkylation of a phenol with a compound of formula V Y—A—≡—B  V wherein A and B are as defined in claim 1 and Y is a leaving group; Step B is the reaction of an aromatic aldehyde with nitromethane; Step C is the reduction of an unsaturated nitrogen compound; Step D is the reaction of an aldehyde or a ketone with hydroxylamine or a hydroxylamine salt; Step E is the hydrolysis of a lower alkyl ester; and Step F is the reaction of a carboxylic acid or an activated carboxylic acid derivative with hydrazoic acid or with a salt of that acid.
 15. A compound of formula VII

wherein R₂, R₃, R₄, R₅, R₆, R₇, R₈, A and B are as defined above.
 16. A process for the preparation of a compound of formula VII according to claim 15, which comprises carrying out the following reaction sequence

wherein the reaction of the amino acid derivative of formula XIII, or of a carboxy-activated derivative thereof, with an amine of formula XII is carried out if desired in the presence of a catalyst, if desired in the presence of an acid-binding agent and if desired in the presence of a diluent; and the reaction of a compound of formula XIV with a compound of formula V is carried out if desired in the presence of an acid-binding agent and if desired in the presence of an inert diluent at temperatures of from −80 to +200° C.; and then the acid hydrolysis of a compound of formula XV with an inorganic or organic acid is carried out if desired in the presence of an inert diluent, at temperatures of from −40 to +150° C.
 17. A compound of formula l according to claim 1 wherein n is the number one; R, and R₈ are methyl; R₃ is (S)-2-propyl; R₂, R₄, R₅, R₆ and R₇ are hydrogen; A is methylene; and B is 4-chlorophenyl which is (S)-2(methylsulfonyl-amino)-3-methyl-butyric acid N-[2-[3-methoxy-4[(3-(4-chlorophenyl)-2-propyn-1yloxy]-phenyl]-ethyl)-amide.
 18. A compound of formula l according to claim 1 wherein n is the number one; R₁ is ethyl; R₃ is (S)-2-propyl; R₂, R₄, R₅, R₆ and R₇ are hydrogen; R₈ is methyl; A is methylene; and B is 4-chlorophenyl. which is (S)-2(ethylsulfonyl-amino)-3-methyl-butyric acid N-[2-[3-methoxy-4[(3-(4-chlorophenyl)-2-propyn-1yloxy]-phenyl]-ethyl)-amide. 